The molecular events underlying chemical transduction in lingual epithelia are not well understood. In this proposal we will measure the electrical, chemical and structural changes that occur in mammalian lingual epithelia in response to chemical stimuli so that models of taste transduction can be tested or formulated as the evidence dictates. The recent discovery that the tongue actively transports ions (1) suggests that previous models of taste transduction that have assumed it to be impermeable to ions and that there are separate pathways for Na+, K+, and H+, and non-electrolytes may have to be modified. Here the active and passive transport properties of dog tongue will be studied by mounting it in a Ussing chamber. The role of taste cells and their proposed receptors in the transduction process will be studied by comparing the passive and active transport behavior of the tongue in the presence and absence of taste papillae. Morphological and intracellular ion changes will be measured using both conventional electron microscopy and electron probe microanalysis. These data will then be used to formulate mechanisms of taste transduction for salts, acids, D and L amino acids, and saccharides. In major goal of this research is to describe the dog tongue as a transporting epithelium. The transport pathways for mono and divalent anions and cations, saccharides, acids, and amino acids will be determined as well as their selectivity isotherms. The effect of ADH, copper, D-penicillamine, nystatin, amiloride, ouabain, C-AMP, intracellular Ca++, and site-specific reagents known to eliminate specific taste responses will be tested for the purpose of determining rate-limiting steps of transport, eliminating particular transport pathways, to determine those cell types that respond to various chemical stimuli, and to determine the role of various hormones in the transduction process. The data we obtained on the voltaged clamped preparation will be correlated with taste perception data which to date have been in substantial agreement. This voltage-clamped epithelial preparation can be used to assay the effect of drugs used to treat patients with taste disorders (such as hypogeusia, which arise at low copper concentrations) and also as a bioassay to identify new artificial tastants.